Matched Sizes of Activating and Inhibitory Receptor/Ligand Pairs Are Required for Optimal Signal Integration by Human Natural Killer Cells
Matched Sizes of Activating and Inhibitory Receptor/Ligand Pairs Are Required for Optimal Signal Integration by Human Natural Killer Cells
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DOI：
10.1371/journal.pone.0015374
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发表时间：
2010-11-05
期刊：
影响因子：
3.7
通讯作者：
Davis, Daniel M.
中科院分区：
文献类型：
--
作者：
Koehler, Karsten;Xiong, Shiqiu;Davis, Daniel M.
有人提出，受体-配体复合物根据其大小在免疫突触内分离或共定位，这对于受体信号转导很重要。在这里，我们着手测试受体-配体复合体尺寸对于人类自然杀伤（NK）细胞对靶细胞免疫监视的重要性。 NK 细胞的激活是通过整合来自激活受体（例如 NKG2D）和抑制受体（例如 KIR2DL1）的信号来调节的。延长 NKG2D 配体 MICA 会降低其触发 NK 细胞激活的能力。相反，KIR2DL1配体HLA-C的延长降低了其抑制NK细胞的能力。虽然正常大小的 HLA-C 在抑制正常长度的 MICA 的激活方面最有效，但只有延长的 HLA-C 才能抑制延长的 MICA 的激活。此外，大小匹配的HLA-C和MICA共定位，而大小不同的HLA-C和MICA分离。这些结果表明受体-配体尺寸在 NK 细胞识别中很重要，并表明激活和抑制受体信号的最佳整合需要受体-配体复合物具有相似的尺寸。
It has been suggested that receptor-ligand complexes segregate or co-localise within immune synapses according to their size, and this is important for receptor signaling. Here, we set out to test the importance of receptor-ligand complex dimensions for immune surveillance of target cells by human Natural Killer (NK) cells. NK cell activation is regulated by integrating signals from activating receptors, such as NKG2D, and inhibitory receptors, such as KIR2DL1. Elongating the NKG2D ligand MICA reduced its ability to trigger NK cell activation. Conversely, elongation of KIR2DL1 ligand HLA-C reduced its ability to inhibit NK cells. Whereas normal-sized HLA-C was most effective at inhibiting activation by normal-length MICA, only elongated HLA-C could inhibit activation by elongated MICA. Moreover, HLA-C and MICA that were matched in size co-localised, whereas HLA-C and MICA that were different in size were segregated. These results demonstrate that receptor-ligand dimensions are important in NK cell recognition, and suggest that optimal integration of activating and inhibitory receptor signals requires the receptor-ligand complexes to have similar dimensions.